Bicyclo[2.2.2]octanes substituted at 1- and/or 4-positions are of great commercial interest. See, for example: (a) Joel G. Whitney, W. A. Gregory, J. C. Kauer, J. R. Roland, Jack A. Snyder, R. E. Benson and E. C. Hermann “Antiviral agents. I. Bicyclo[2.2.2]octan- and -oct-2-enamines” J. Med. Chem., 1970, 13, 254-60; (b) U.S. Pat. No. 3,546,290. (c) “4-Pyridyl and 4-(substituted-pyridyl) bicyclo[2.2.2]octane-1-amines” U.S. Pat. No. 3,367,941; and (d) Bicyclo [2.2.2] Acid GPR120 Modulators, US Pat. Appl. 2016/0039780.
Unfortunately, the bridgehead substituents of various bicyclic systems inclusive of the bicyclo[2.2.2]octane system are inert to nucleophilic substitution. Therefore, it would be useful to develop simple methods of preparation of the bridgehead bicyclo[2.2.2]octane derivatives. 1,4-Diacetoxybicyclo[2.2.2]octane is particularly interesting because it is a potential starting material for the preparation of various bridgehead bicyclo[2.2.2]octane derivatives. By way of example, U.S. Pat. No. 6,649,600 teaches various adenosine receptor antagonists, such compounds containing bridgehead bicyclo[2.2.2]octane substituents, which can be prepared from 1,4-diacetoxybicyclo[2.2.2]octane.
Bicyclo[2.2.2]octane derivatives also serve as important intermediates in the synthesis of natural products such as terpenes and alkaloids. (see, for example, Org. Biomol. Chem., 2006, 4, 2304-2312). They are also important building blocks for therapeutic agents for the treatment of metabolic syndrome (see, for example, Bioorg. Med. Chem. Lett., 2005, 15, 5266-5269) and other diseases (Org. Biomol. Chem., 2006, 4, 2304-2312).
Moreover, bicyclo[2.2.2]octane diols and diacids are useful as specialty monomers for certain polymers. See, for example, (a) G.B. 1,024,487; (b) J. Polym. Sci. Part A, 2010, Vol. 48, pp. 2162-2169; (c) U.S. Pat. No. 3,256,241; (d) U.S. Pat. No. 3,081,334; (e) Mol. Cryst. Liq. Cryst., 1981, Vol. 66, pp. 267-282; (f) J. Polym. Sci. A, 1994, Vol 32, pp. 2953-2960; and (g) J. Am. Chem. Soc. 1970, Vol 92, pp. 1582-1586.
Existing methods for the production of bicyclo[2.2.2]octane 1,4-substituted derivatives often involve expensive and toxic reagents, salt-forming reactions, costly reaction conditions, and suffer from poor net yields. (See, for example, Kopecký, Jan; Jaroslav, S̆mejkal; and Vladimír, Hanus̆; Synthesis of bridgehead bicyclo[2.2.2]octanols, Coll. Czech. Chem. Commun. 1981, 46, 1370-1375.) The reaction sequence is given in Scheme 1 below. Acid-catalyzed reaction of isopropenyl acetate with 1,4-cyclohexanedione provides (besides 1,4-diacetoxy-1,4-cyclohexadiene) 1,4-diacetoxy-O-cyclohexadiene (1) which undergoes diene cycloaddition with maleic anhydride to provide 1,4-diacetoxybicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic acid anhydride (H). Hydrogenation of (II) provides the saturated III which was hydrolyzed to the corresponding dicarboxylic acid (IV). Oxidative decarboxylation of (IV) with lead tetraacetate in pyridine in the presence of oxygen gave 1,4-diacetoxybicyclo[2.2.2]oct-2-ene (V) which upon hydrogenation gave diacetate (VI). The overall yield was reported to be 28-31%.

Beginning with 1,4-CHDM (1,4-cyclohexane dimethanol), a two-step conversion to 1,4-dimethylene cyclohexane is known (Scheme 2). (See J. Am. Chem. Soc., 1953, 75, 4780-4782.)
